AXS-05 for Depression

Recruiting at 36 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Axsome Therapeutics, Inc.

Must not be taking: Auvelity

Disqualifiers: Other AXS-05 studies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment, AXS-05 (a combination of dextromethorphan and bupropion), in preventing the recurrence of depression in individuals with major depressive disorder (MDD) who have already responded well to it. Participants will either continue with AXS-05 or switch to bupropion to determine which medication better prevents depressive symptoms. Individuals diagnosed with MDD for at least four weeks, without psychotic symptoms, may be suitable for this trial. As a Phase 4 trial, this research involves an FDA-approved treatment, aiming to understand its benefits for a broader patient population.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for these treatments?

Research has shown that AXS-05, a combination of dextromethorphan and bupropion, is safe for treating major depressive disorder. Studies have found that most people tolerate AXS-05 well. Long-term studies, in particular, indicate it can be used safely over time without major issues.

Some side effects occurred, but they were usually mild and manageable. These studies offer reassuring evidence about the safety of AXS-05 for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard antidepressants like SSRIs and SNRIs, AXS-05 is unique because it combines two active ingredients: dextromethorphan and bupropion. This combination works differently by targeting both the NMDA receptor and the sigma-1 receptor, potentially offering faster and more effective relief from depression symptoms. Researchers are excited about AXS-05 because it might provide a new option for patients who haven’t responded well to traditional antidepressants, offering a fresh hope for quicker and more comprehensive symptom management.

What evidence suggests that AXS-05 might be an effective treatment for depression?

Research shows that AXS-05, a combination of dextromethorphan and bupropion, helps treat major depressive disorder (MDD). In this trial, participants may receive AXS-05, which studies have found reduces depression symptoms more effectively than bupropion alone. Specifically, one study showed that 46.5% and 39.5% of participants experienced complete symptom relief, a higher rate than with bupropion alone. Participants began feeling better as soon as one week after starting treatment. AXS-05 is approved for treating MDD, indicating its proven effectiveness for this condition. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals currently diagnosed with Major Depressive Disorder (MDD) without psychotic features, experiencing a depressive episode lasting at least 4 weeks. It's not open to those who've been in AXS-05 studies before, used investigational drugs or Auvelity within the last month, or can't follow study procedures.

Inclusion Criteria

I have been experiencing a major depressive episode for at least 4 weeks.

I have been diagnosed with major depression without experiencing psychosis.

Exclusion Criteria

Medically inappropriate for study participation in the opinion of the investigator

I haven't taken any experimental drugs or used experimental devices in the last 30 days, nor have I been prescribed Auvelity.

Unable to comply with study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

Eligible subjects receive open-label AXS-05 for 10 weeks to monitor response and remission

10 weeks

Double-blind Treatment

Randomized subjects receive double-blind treatment with either AXS-05 or bupropion for 26 weeks or until relapse

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AXS-05
• Bupropion

Trial Overview The study tests if AXS-05 is better than Bupropion at preventing relapse of depression in people whose symptoms improved after taking AXS-05. Participants are randomly assigned to either drug and won't know which one they're getting during the trial.

How Is the Trial Designed?

Group I: AXS-05 Experimental Treatment 1 Intervention

AXS-05 tablets, taken twice daily

Group II: Bupropion Active Control 1 Intervention

Bupropion tablets, taken twice daily

AXS-05 is already approved in United States for the following indications:

Approved in United States as Auvelity for:

• Major depressive disorder

Who Is Running the Clinical Trial?

Axsome Therapeutics, Inc.

Lead Sponsor

Trials

34

Recruited

11,600+

Published Research Related to This Trial

Dextromethorphan/bupropion, a fixed-dose combination medication, was approved in August 2022 for treating major depressive disorder (MDD) in adults, highlighting its efficacy as a new treatment option.

The combination works by utilizing dextromethorphan as an NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion enhances the bioavailability of dextromethorphan, potentially improving therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: First Approval. Keam, SJ.[2022]

Dextromethorphan (DXM) has been repurposed multiple times, showing its versatility as a treatment for cough, pseudobulbar affect, and now major depressive disorder when combined with bupropion.

The oral formulation of dextromethorphan and bupropion is noted for its rapid action and favorable safety profile, making it a promising option for treating major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan: From Cough Suppressant to Antidepressant. Kverno, K.[2022]

In a phase 2 trial involving 80 patients with major depressive disorder, dextromethorphan-bupropion (AXS-05) showed a significantly greater reduction in depression symptoms compared to bupropion, with a mean change in MADRS score of -13.7 points versus -8.8 points over 6 weeks.

Dextromethorphan-bupropion also resulted in higher remission rates (46.5% vs. 16.2% at week 6) and response rates (60.5% vs. 40.5% at week 6), while being generally well tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. Tabuteau, H., Jones, A., Anderson, A., et al.[2022]

Esketamine, an NMDA antagonist administered intranasally, has been approved for treatment-resistant depression, highlighting the need for faster-acting antidepressants with different mechanisms than traditional monoamine-targeting drugs.

Dextromethorphan/bupropion is an investigational medication being developed as a potential rapid-onset treatment for depression, aiming to address the limitations of current therapies that often take weeks to show effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity. Stahl, SM.[2021]

Auvelity, a combination of dextromethorphan and bupropion, is approved for treating major depressive disorder in adults, but it carries a boxed warning for increased risk of suicidal thoughts and behaviors in younger patients.

Common side effects include dizziness, nausea, and headache, with a risk of seizures at higher doses, highlighting the importance of careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Combination Drug for Depression. Aschenbrenner, DS.[2023]

In a phase 3 trial involving 327 patients with major depressive disorder, AXS-05 (dextromethorphan-bupropion) significantly improved depressive symptoms compared to placebo, with effects noticeable as early as week 1.

The treatment led to a remission rate of 39.5% compared to 17.3% for placebo, and was generally well tolerated, with no serious side effects like weight gain or increased sexual dysfunction reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). Iosifescu, DV., Jones, A., O'Gorman, C., et al.[2022]

Dextromethorphan-bupropion (Auvelity) is an FDA-approved treatment for major depressive disorder that has shown significant efficacy in reducing depression scores in phase 3 trials, with effects noticeable within two weeks.

The treatment is well-tolerated, with mild-to-moderate side effects, and long-term studies indicate high remission rates of nearly 70% and response rates over 80%, making it a promising option for fast-acting depression relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder. McCarthy, B., Bunn, H., Santalucia, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12370225/

Efficacy and safety of dextromethorphan–bupropion ... The findings indicate superior efficacy of the dextromethorphan–bupropion combination, with remission rates of 46.5% and 39.5%, compared to 16.2 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35649167/

Efficacy and Safety of AXS-05 (Dextromethorphan ... Treatment with dextromethorphan-bupropion (AXS-05) resulted in significant improvements in depressive symptoms compared to placebo starting 1 week after ...

3. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.21080800

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major ... In patients with major depression, dextromethorphan-bupropion (AXS-05) significantly improved depressive symptoms compared with bupropion and was generally ...

4. auvelityhcp.com auvelityhcp.com/efficacy

Efficacy: Clinical Study Results Effect of AXS-05 (dextromethorphan-bupropion) in major depressive disorder: a randomized double-blind controlled trial. Am J Psychiatry. 2022;179(7):490-499. 13 ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/215430Orig1s000MultidisciplineR.pdf

215430Orig1s000 - accessdata.fda.gov The proposed indication for AXS-05 is for the treatment of major depressive disorder (MDD). The proposed dosing regimen for Auvelity tablets ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40686359/

Efficacy and safety of dextromethorphan-bupropion ... The findings indicate superior efficacy of the dextromethorphan-bupropion combination, with remission rates of 46.5% and 39.5%, compared to 16.2 ...

7. auvelityhcp.com auvelityhcp.com/long-term-data

Long-Term Data - AUVELITY (dextromethorphan-bupropion) Sustained efficacy and long-term safety of AXS-05, an oral NMDA receptor antagonist, in major depressive disorder: COMET study results. Poster presented at ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04039022

NCT04039022 | Open-Label Safety Study of AXS-05 in ... A multi-center, open-label, long-term study to evaluate the safety and efficacy of AXS-05 in patients with major depressive disorder, including treatment ...